Stem Cells: A Review Encompassing the Literature with a Special Focus on the Side-Lined Miraculous Panacea; Pre-Morula Stem Cells

Author(s): Aryendu K. Saini*, Rakesh Saini, Himanshu Bansode, Anurag Singh, Lalita Singh

Journal Name: Current Stem Cell Research & Therapy

Volume 15 , Issue 4 , 2020

Become EABM
Become Reviewer

Abstract:

Stem cells are the undifferentiated cells in the body that possess the ability to differentiate and give rise to any type of cells in the body. In recent years, there has been a growing interest in therapies involving stem cells as different treatment methods got developed. Depending on the source, there are two major kinds of stem cells, embryonic and adult stem cells. The former type is found in the embryo at the different developmental stages before the implantation and excels the latter owing to pluripotency. On the premise of the attributes of stem cells, they are touted as the "panacea for all ills" and are extensively sought for their potential therapeutic roles. There are a lot of robust pieces of evidence that have proved to cure the different ailments in the body like Huntington disease, Parkinson's disease, and Spinal cord injury with stem cell therapy but associated with adverse effects like immune rejection and teratoma formation. In this regard, the pre-morula (isolated at an early pre-morula stage) stem cells (PMSCs) are one of its kind of embryonic stem cells that are devoid of the aforementioned adverse effects. Taking the beneficial factor into account, they are being used for the treatment of disorders like Cerebral palsy, Parkinson's disorder, Aplastic anemia, Multiple sclerosis and many more. However, it is still illegal to use stem cells in the abovementioned disorders. This review encompasses different stem cells and emphasizes on PMSCs for their uniqueness in therapy as no other previously published literature reviews have taken these into consideration. Later in the review, current regulatory aspects related to stem cells are also considered.

Keywords: Human embryonic stem cell, morula, parkinson's disease, blastocyst inner cell mass, diabetes mellitus, type 2, transcription factors, cell differentiation, teratoma.

[1]
Rajabzadeh N, Fathi E, Farahzadi R. Stem cell-based regenerative medicine. Stem Cell Investig 2019; 6: 19.
[http://dx.doi.org/10.21037/sci.2019.06.04] [PMID: 31463312]
[2]
Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther 2019; 10(1): 68.
[http://dx.doi.org/10.1186/s13287-019-1165-5] [PMID: 30808416]
[3]
De Luca M, Aiuti A, Cossu G, Parmar M, Pellegrini G, Robey PG. Advances in stem cell research and therapeutic development. Nat Cell Biol 2019; 21(7): 801-11.
[http://dx.doi.org/10.1038/s41556-019-0344-z] [PMID: 31209293]
[4]
Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282(5391): 1145-7.
[http://dx.doi.org/10.1126/science.282.5391.1145] [PMID: 9804556]
[5]
Eguizabal C, Aran B, Chuva de Sousa Lopes SM, et al. Two decades of embryonic stem cells: a historical overview. Hum Reprod Open 2019; 2019(1): hoy024
[http://dx.doi.org/10.1093/hropen/hoy024] [PMID: 30895264]
[6]
Post Y, Clevers H. Defining Adult Stem Cell Function at Its Simplest: The Ability to Replace Lost Cells through Mitosis. Cell Stem Cell 2019; 25(2): 174-83.
[http://dx.doi.org/10.1016/j.stem.2019.07.002] [PMID: 31374197]
[7]
Singh A, Yadav CB, Tabassum N, Bajpeyee AK, Verma V. Stem cell niche: Dynamic neighbor of stem cells. Eur J Cell Biol 2019; 98(2-4): 65-73.
[http://dx.doi.org/10.1016/j.ejcb.2018.12.001] [PMID: 30563738]
[8]
Mao AS, Mooney DJ. Regenerative medicine: Current therapies and future directions. Proc Natl Acad Sci USA 2015; 112(47): 14452-9.
[http://dx.doi.org/10.1073/pnas.1508520112] [PMID: 26598661]
[9]
Gutierrez-Aranda I, Ramos-Mejia V, Bueno C, et al. Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection. Stem Cells 2010; 28(9): 1568-70.
[http://dx.doi.org/10.1002/stem.471] [PMID: 20641038]
[10]
de Almeida PE, Ransohoff JD, Nahid A, Wu JC. Immunogenicity of pluripotent stem cells and their derivatives. Circ Res 2013; 112(3): 549-61.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.249243] [PMID: 23371903]
[11]
Bar S, Benvenisty N. Epigenetic aberrations in human pluripotent stem cells. EMBO J 2019; 38(12): e101033
[http://dx.doi.org/10.15252/embj.2018101033] [PMID: 31088843]
[12]
Shroff G. Establishment and characterization of a neuronal cell line derived from a 2-cell stage human embryo: clinically tested cell-based therapy for neurological disorders. Int J Recent Sci Res 2015; 6(4): 3730-8.
[13]
[14]
Strelchenko N, Verlinsky O, Kukharenko V, Verlinsky Y. Morula-derived human embryonic stem cells. Reprod Biomed Online 2004; 9(6): 623-9.
[http://dx.doi.org/10.1016/S1472-6483(10)61772-5] [PMID: 15670408]
[15]
Mittal S. Stem cell research: The India perspective. Perspect Clin Res 2013; 4(1): 105-7.
[http://dx.doi.org/10.4103/2229-3485.106408] [PMID: 23533992]
[16]
Choi K, Choi Y, Hong S. Stem cell transplantation for Huntington’s diseases 2018; 133: 104-.
[http://dx.doi.org/10.1016/j.ymeth.2017.08.017]
[17]
Agarwal S, Holton KL, Lanza R. Efficient differentiation of functional hepatocytes from human embryonic stem cells. Stem Cells 2008; 26(5): 1117-27.
[http://dx.doi.org/10.1634/stemcells.2007-1102] [PMID: 18292207]
[18]
Shroff G. Therapeutic potential of human embryonic stem cells in type 2 diabetes mellitus. World J Stem Cells 2016; 8(7): 223-30.
[http://dx.doi.org/10.4252/wjsc.v8.i7.223] [PMID: 27468331]
[19]
Xiao B, Ng HH, Takahashi R, Tan EK. Induced pluripotent stem cells in Parkinson’s disease: scientific and clinical challenges. J Neurol Neurosurg Psychiatry 2016; 87(7): 697-702.
[http://dx.doi.org/10.1136/jnnp-2015-312036] [PMID: 26833176]
[20]
Lahiry S, Choudhury S, Sinha R, Chatterjee S. The National Guidelines for Stem Cell Research (2017): What academicians need to know? Perspect Clin Res 2019; 10(4): 148-54.
[http://dx.doi.org/10.4103/picr.PICR_23_18] [PMID: 31649863]
[21]
FDA Warns About Stem Cell Therapies [Internet]. FDA 2019.https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies
[22]
Boroviak T, Loos R, Bertone P, Smith A, Nichols J. The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification. Nat Cell Biol 2014; 16(6): 516-28.
[http://dx.doi.org/10.1038/ncb2965] [PMID: 24859004]
[23]
Reik W, Surani MA. Germline and Pluripotent Stem Cells. Cold Spring Harb Perspect Biol 2015; 7(11): a019422
[http://dx.doi.org/10.1101/cshperspect.a019422] [PMID: 26525151]
[24]
Musgrove C, Jansson LI, Stone MD. New perspectives on telomerase RNA structure and function. Wiley Interdiscip Rev RNA 2018; 9(2): 1-11.
[http://dx.doi.org/10.1002/wrna.1456] [PMID: 29124890]
[25]
Pfeffer PL. Building Principles for Constructing a Mammalian Blastocyst Embryo. Biology (Basel) 2018; 7(3): 1-24.
[http://dx.doi.org/10.3390/biology7030041] [PMID: 30041494]
[26]
Shroff G, Gupta R. Human embryonic stem cells in the treatment of patients with spinal cord injury. Ann Neurosci 2015; 22(4): 208-16.
[http://dx.doi.org/10.5214/ans.0972.7531.220404] [PMID: 26526627]
[27]
Shroff G, Seidel PH. Use of Human Embryonic Stem Cells in the Treatment of Parkinsons Disease: A Case Report. Int J Emerg Ment Health 2015; 17(3): 661-3.
[PMID: 26568701]
[28]
ReoStem. A new paradigm in allogenic stem cells http://www.reostem.com (Accessed Feb 1, 2020).
[29]
Shroff G, Srivastav A, Shroff R. Human Embryonic Stem Cell Derived from Early Stage Fertilized Ovum: Non Immunogenic and Universal, Neuronal and Non-neuronal Cell Lines. Int J Stem Cells 2018; 11(1): 105-10.
[http://dx.doi.org/10.15283/ijsc17064] [PMID: 29699383]
[30]
Vazin T, Freed WJ. Human embryonic stem cells: derivation, culture, and differentiation: a review. Restor Neurol Neurosci 2010; 28(4): 589-603.
[http://dx.doi.org/10.3233/RNN-2010-0543] [PMID: 20714081]
[31]
Shroff G, Vatsa D. Cell Viability of Human Embryonic Stem Cells Stored for a Period of 9 Years. Exp Clin Transplant 2017; 15(3): 344-9.
[PMID: 27938317]
[32]
Science And Technology Select Committee [Internet]. ParliamentUK [2020 Feb 1]. https://www.parliament.uk/documents/lords-committees/science-technology/RegenerativeMedicine/RegenMed.pdf
[33]
Sobhani A, Khanlarkhani N, Baazm M, et al. Multipotent Stem Cell and Current Application. Acta Med Iran 2017; 55(1): 6-23.
[PMID: 28188938]
[34]
Kögler G, Sensken S, Airey JA, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 2004; 200(2): 123-35.
[http://dx.doi.org/10.1084/jem.20040440] [PMID: 15263023]
[35]
Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114(6): 763-76.
[http://dx.doi.org/10.1016/S0092-8674(03)00687-1] [PMID: 14505575]
[36]
Liete CF, Almeida TR, Lopes CS, et al. Multipotent stem cells of the heart-do they have therapeutic promise? Front Physiol 2015; 6(123): 1-17.
[37]
Mosher KI, Schaffer DV. Proliferation versus Differentiation: Redefining Retinoic Acid’s Role. Stem Cell Reports 2018; 10(6): 1673-5.
[http://dx.doi.org/10.1016/j.stemcr.2018.05.011] [PMID: 29874625]
[38]
Shen H, Wang Y, Zhang Z, Yang J, Hu S, Shen Z. Mesenchymal Stem Cells for Cardiac Regenerative Therapy: Optimization of Cell Differentiation Strategy. Stem Cells Int 2015; 2015: 524756
[http://dx.doi.org/10.1155/2015/524756] [PMID: 26339251]
[39]
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131(5): 861-72.
[http://dx.doi.org/10.1016/j.cell.2007.11.019] [PMID: 18035408]
[40]
Bedel A, Beliveau F, Lamrissi-Garcia I, et al. Preventing Pluripotent Cell Teratoma in Regenerative Medicine Applied to Hematology Disorders. Stem Cells Transl Med 2017; 6(2): 382-93.
[http://dx.doi.org/10.5966/sctm.2016-0201] [PMID: 28191782]
[41]
Baker CL, Pera MF. Capturing Totipotent Stem Cells. Cell Stem Cell 2018; 22(1): 25-34.
[http://dx.doi.org/10.1016/j.stem.2017.12.011] [PMID: 29304340]
[42]
Wu H, Zhang Y. Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell 2014; 156(1-2): 45-68.
[http://dx.doi.org/10.1016/j.cell.2013.12.019] [PMID: 24439369]
[43]
Rougier N, Bourc’his D, Gomes DM, et al. Chromosome methylation patterns during mammalian preimplantation development. Genes Dev 1998; 12(14): 2108-13.
[http://dx.doi.org/10.1101/gad.12.14.2108] [PMID: 9679055]
[44]
Kohli RM, Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 2013; 502(7472): 472-9.
[http://dx.doi.org/10.1038/nature12750] [PMID: 24153300]
[45]
Aguirre-Lavin T, Adenot P, Bonnet-Garnier A, et al. 3D-FISH analysis of embryonic nuclei in mouse highlights several abrupt changes of nuclear organization during preimplantation development. BMC Dev Biol 2012; 12: 30.
[http://dx.doi.org/10.1186/1471-213X-12-30] [PMID: 23095683]
[46]
Banerjee A, Kamath VV, Sundaram L, et al. OCT4 and SOX2 are reliable markers in detecting stem cells in odontogenic lesions 2016; (1): 16-21.
[47]
Zangrossi S, Marabese M, Brogini M, et al. Oct-4 Expression in Adult Human Differentiated Cells Challenges Its Role as a Pure Stem Cell Marker 2007; 25(7): 1675-80.
[48]
Sahni V, Kessler JA. Stem cell therapies for spinal cord injury. Nat Rev Neurol 2010; 6(7): 363-72.
[http://dx.doi.org/10.1038/nrneurol.2010.73] [PMID: 20551948]
[49]
Sezer N, Akkuş S, Uğurlu FG. Chronic complications of spinal cord injury. World J Orthop 2015; 6(1): 24-33.
[http://dx.doi.org/10.5312/wjo.v6.i1.24] [PMID: 25621208]
[50]
Dietrich WD, Levi AD, Wang M, Green BA. Hypothermic treatment for acute spinal cord injury. Neurotherapeutics 2011; 8(2): 229-39.
[http://dx.doi.org/10.1007/s13311-011-0035-3] [PMID: 21416406]
[51]
Young NS, Scheinberg P, Calado RT. Aplastic anemia. Curr Opin Hematol 2008; 15(3): 162-8.
[http://dx.doi.org/10.1097/MOH.0b013e3282fa7470] [PMID: 18391779]
[52]
Georges GE, Doney K, Storb R. Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment. Blood Adv 2018; 2(15): 2020-8.
[http://dx.doi.org/10.1182/bloodadvances.2018021162] [PMID: 30108110]
[53]
Suzuki N, Yamazaki S, Yamaguchi T, et al. Generation of engraftable hematopoietic stem cells from induced pluripotent stem cells by way of teratoma formation. Mol Ther 2013; 21(7): 1424-31.
[http://dx.doi.org/10.1038/mt.2013.71] [PMID: 23670574]
[54]
Shroff G, Gupta R, Zadeng L. Human embryonic stem cell therapy for aplastic anemia. Clin Case Rep 2017; 5(6): 919-22.
[http://dx.doi.org/10.1002/ccr3.950] [PMID: 28588839]
[55]
Schwarz S, Knorr C, Geiger H, Flachenecker P. Complementary and alternative medicine for multiple sclerosis. Mult Scler 2008; 14(8): 1113-9.
[http://dx.doi.org/10.1177/1352458508092808] [PMID: 18632773]
[56]
Robertson D, Moreo N. Disease-Modifying Therapies in Multiple Sclerosis: Overview and Treatment Considerations. Fed Pract 2016; 33(6): 28-34.
[PMID: 30766181]
[57]
Harlow DE, Honce JM, Miravalle AA. Remyelination Therapy in Multiple Sclerosis 2015; 6: 1-13.
[58]
Shroff G. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease. Am J Case Rep 2016; 17: 944-9.
[http://dx.doi.org/10.12659/AJCR.899745] [PMID: 27956736]
[59]
Alexander GE. Biology of Parkinson’s disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues Clin Neurosci 2004; 6(3): 259-80.
[PMID: 22033559]
[60]
Zhang J, Wang X, Li J, et al. The Preclinical Research Progress of Stem Cells Therapy in Parkinson’s Disease. BioMed Res Int 2016; 2016: 5683097
[http://dx.doi.org/10.1155/2016/5683097] [PMID: 27379248]
[61]
O’Shea TM. Diagnosis, treatment, and prevention of cerebral palsy. Clin Obstet Gynecol 2008; 51(4): 816-28.
[http://dx.doi.org/10.1097/GRF.0b013e3181870ba7] [PMID: 18981805]
[62]
Abi Chahine NH, Wehbe TW, Hilal RA, Zoghbi VV, Melki AE, Habib EB. Treatment of Cerebral Palsy with Stem Cells: A Report of 17 Cases. Int J Stem Cells 2016; 9(1): 90-5.
[http://dx.doi.org/10.15283/ijsc.2016.9.1.90] [PMID: 27426090]
[63]
Shroff G, Gupta A, Barthakur JK. Therapeutic potential of human embryonic stem cell transplantation in patients with cerebral palsy. J Transl Med 2014; 12: 318.
[http://dx.doi.org/10.1186/s12967-014-0318-7] [PMID: 25496119]
[64]
Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocrinol Metab 2016; 20(4): 546-51.
[http://dx.doi.org/10.4103/2230-8210.183480] [PMID: 27366724]
[65]
Lodi D, Iannitti T, Palmieri B. Stem cells in clinical practice: applications and warnings. J Exp Clin Cancer Res 2011; 30: 9.
[http://dx.doi.org/10.1186/1756-9966-30-9] [PMID: 21241480]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 4
Year: 2020
Page: [379 - 387]
Pages: 9
DOI: 10.2174/1574888X15666200311141731
Price: $65

Article Metrics

PDF: 12
HTML: 1